The Association Of Iron Status With Diabetes Mellitus And 10-year Risk Of Atherosclerotic Cardiovascular Disease In Patients With Hypertension

Atherosclerotic cardiovascular disease(ASCVD)and diabetes mellitus(DM)are the leading causes of death worldwide.Scientific evidence suggests an association between abnormal iron status and DM as well as ASCVD.Hypertension is now highly prevalent and increasing worldwide,with DM and ASCVD as its major complications.Previous studies have indicated that serum ferritin(SF)and haemoglobin(Hb)levels are significantly higher in hypertensive patients than in those with normal blood pressure.Abnormal iron status may be a potential key factor in the development of hypertensive complications.However,there are limited studies on hypertensive patients.Therefore,this study firstly visualized the research on the relationship of iron status with DM and ASCVD through bibliometric analysis.Then,epidemiological data were used to analyze the association of iron status(SF and Hb)with DM and10-year ASCVD risk scores in hypertensive patients,to provide a theoretical basis for the prevention and control of hypertensive complications.Part I A bibliometric analysis of the association of iron status with diabetes mellitus and atherosclerotic cardiovascular disease Objective:To analyse the current status and progress of research on the association of iron status with DM and ASCVD,and provide a theoretical framework for the subsequent empirical evidence.Methods:A bibliometric analysis was conducted using Cite Space 5.7.R5 software to visualise the information on 1,677 publications on the association between iron status and DM and 3,776 publications on the association between iron status and ASCVD in the Web of Science database from 1997 to 2020.The analysis includes spatial and temporal distribution characteristics,literature co-citation analysis and keyword co-occurrence.Results:1.The number of annual publications on the association of iron status with DM and ASCVD has been increasing.Research in Europe and the United States started early,with a large number of outputs and centrality.In recent years,although China has increased its investment and the number of outputs,the centrality is low.2.In the field of iron status in relation to DM and ASCVD,studies have focused on patients with haemochromatosis,blood donors and the general population.3.The hot topics of the research on the association of iron status with DM and ASCVD show a shift from iron overload to iron deficiency(ID).Both of them may have adverse effects on glucose metabolism and cardiovascular health.Conclusions:There has been a shift in the hot spots of research on the association of iron status with DM and ASCVD,with a gradual progression from iron overload to ID.Currently,limited studies have been conducted on hypertensive patients.Part II The association between iron status and diabetes mellitus in patients with hypertension Objective:To explore the association between iron status and DM in patients with hypertension,and provide a theoretical basis for the prevention of hypertensive diabetes.Methods:This study was based on data from the “Community-based Screening and Intervention Programme for People at High Risk of Stroke” in Nanshan District,Shenzhen in 2017.A total of 1,787 hypertensive people were selected as the research,SF and Hb were used as indicators of iron status.DM was diagnosed when fasting blood glucose ≥ 7.0 mmol/L and/or a previous clinical diagnosis of DM.Glycosylated haemoglobin≥6.5%was used as one of the diagnostic criteria for DM to conduct sensitivity analysis.Pearson correlation was fitted to explore the correlation between SF and Hb.SF below 30 ng/m L was termed ID.Hb levels below 130 g/L in men and120 g/L in women were defined as anaemia.The concentration of SF and Hb was considered continuous variables and categorized into quartiles according to their sex-specific distribution.Multiple-variable logistic regression models were used to explore the association between iron status and DM,and restricted cubic splines were used to illustrate its dose-effect curve.Stratified and interaction analyses were used to explore the potential effects of modification.Sensitivity analysis was performed by excluding people with C reactive protein(CRP)higher than 5 mg/L.Results:1.The prevalence of DM in hypertensive patients increased with the increase of age and body mass index(P linear trend < 0.05),and the overall rate was 22.2%;the new detection rates of DM in 40-49 years old and obese hypertensive patients were higher,respectively 18.9 % and 16.7%.2.There was a weak positive correlation between Hb and SF.The prevalence of ID and anaemia in hypertensive patients was 6.5% and 14.4%,respectively.3.The logistic regression model showed that elevated SF concentration was associated with an increased prevalence of DM.After adjusting for multiple covariates,the OR(95%CI)value was 1.55(1.12,2.16)for the highest quantile of SF compared with the lowest quantile.Restricted cubic spline indicated that the association between SF and DM in hypertensive patients was nonlinear(P-nonlinearity = 0.035).However,no association was found between Hb and DM.4.In stratified analyses,the association between iron status and DM was not affected by covariate(P interaction > 0.05).5.Sensitivity analyses that excluded patients with CRP above 5 mg/L or combined with glycated haemoglobin ≥ 6.5% as one of the diagnostic criteria for DM showed that elevated SF levels were associated with an increased prevalence of DM and that Hb concentration was not associated with DM.Conclusions:Elevated SF in hypertensive patients was associated with increased prevalence of DM,but the association between Hb and DM was not observed.Part III Association between iron status and 10-year risk of atherosclerotic cardiovascular disease in patients with hypertension Objective:To explore the association between iron status and 10-year ASCVD risk score in patients with hypertension,and provide a theoretical basis for the prevention of ASCVD in a hypertensive population.Methods:The source of data and definition are the same as those in Part II.A total of 1,426 hypertensive patients aged 35-74 years and without ASCVD were selected as the study subjects.The Prediction for ASCVD Risk in China model was used to calculate the 10-year ASCVD risk score.As sex affects the association between iron status and ASCVD risk score,SF and Hb were grouped according to sex-specific tertile.The generalized linear model was used to explore the association between iron status and10-year ASCVD risk score.Sensitivity analysis was performed by excluding those with CRP above 5 mg/L.Stratified and interaction analyses were used to explore whether CRP was a potential effect modifier.Results:1.The median 10-year ASCVD risk score for hypertensive patients was 5.3%based on the prediction model,with 5.7% and 4.9% for men and women,respectively.2.There was a weak positive correlation between Hb and SF.The prevalence of ID and anaemia was 1.7% and 9.9% in men,and 12.9% and 17.4% in women,respectively.3.In men,iron status showed a U-shape association with the 10-year ASCVD risk score.From the lowest tertile to the highest tertile,the adjusted β values for SF were1.00,-0.99(95% CI:-1.65,-0.33)and-0.22(95% CI:-0.88,0.44),for Hb were 0.00,-0.74(95% CI:-1.41,-0.08)and-0.77(95% CI:-1.46,-0.08).In women,after adjusting for multiple variables,each unit increased in log-transformed SF as well as Hb was found to be associated with a 1.22(95% CI: 0.97,1.48)and 0.04(95% CI:0.02,0.07)increase in ASCVD risk score,respectively.Sensitivity analyses showed a robust sex-specific association between iron status and ASCVD.4.There was a significant interaction between iron status and CRP in relation to 10-year ASCVD risk in hypertensive women(P interaction<0.05).A stronger association between iron status and ASCVD was observed in patients with CRP above the median than in those with CRP below the median.Conclusions:There was a sex-specific association between iron status and predicted 10-year ASCVD risk score: a U-shape curve in men and a linear positive association in women.